A critical review of styrene and styrene-7,8-oxide genotoxicity literature: an update

Recent studies investigating mutagenic/cytogenetic effects of styrene and styrene-7,8-oxide (SO) were reviewed to update published critical evaluations of these data from 2019. Transcriptomics studies relevant to styrene/SO genotoxicity were included from a broader timeframe, as they were not reviewed previously. Data on primary DNA damage endpoints (single strand breaks, comet assay, oxidative adducts) were considered when these were included in the publications reviewed. Several recent investigations in mice and rats addressed a significant data-gap for gene mutations from <i>in vivo</i> models. These Organization for Economic Co-operation and Development (OECD) OECD guideline-compliant investigations revealed no evidence of mutagenicity in multiple tissues of mouse (lung, liver, stomach, duodenum, and bone marrow) or in bone marrow of rat. These data, with negative results for DNA damage and micronuclei from the recent repeat-dose rodent studies, add substantially to the weight-of-evidence conclusion that styrene is not an <i>in vivo</i> mutagen or clastogen/aneugen. Results from recently published epidemiological studies have not provided any additional data supporting a conclusion that styrene exposure at the workplace causes increased frequencies of cytogenetic damage. In conclusion, while styrene (under certain conditions) and SO have the potential to induce mutagenic or cytogenetic effects <i>in vitro</i>, there is no convincing evidence for these effects in experimental animals or humans.